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Objectives: This study aimed to determine the effects of propolis on immune mediators and tissue histopathology in rats with L-arginine-induced acute pancreatitis (AP). Methods: This study was conducted at Imam Abdulrahman Bin Faisal University, Dammam, Saudia Arabia between September and November 2017. A total of 24 male albino Wistar rats were divided into three equal groups. Group one was the negative control, group two was the positive control (L-arginine-induced AP) and group three received treatment (L-arginineinduced AP and propolis). The rats in group three were treated with 100 mg/kg propolis for seven days after AP induction. Pancreatic tissue was evaluated histologically and levels of interleukin (IL)-6, IL-22 and IL-1β and tumour necrosis factor-alpha (TNF-α) were measured. Results: Propolis reduced the quanitity of proinflammatory molecules (TNF-α, IL-1β and IL-6) in group three compared to group two, significantly increased the overall antiinflammatory effect of IL-22 (P <0.005) and reduced interstitial inflammation and neutrophil cell infiltration of the pancreatic tissues. Conclusion: Propolis may exert a therapeutic effect in AP. Further studies are required to demonstrate the mechanisms of propolis in AP